Studies of the structure and function of lysosomes will continue in four areas: 1) studies of the uptake, storage, and membrane-action of agents which stabilize or labilize the membranes of lysosomes; 2) studies of the regulation of endocytosis, intracellular distribution and degradation of antigenic macromolecules by macrophages; especially of the effects of cyclic AMP on the vacuolar system; 3) the formation of a lysosome model (liposome) composed of defined phospholipids, cholesterol, and membrane proteins which will enclose lysozyme, and 4) the effects of lysosomal proteases upon the proteins in intact nuclei or chromatin which retard the access of RNA polymerase to DNA. Each of these studies is a natural extension of previous work and is designed to answer questions raised by these earlier observations. Together they should elucidate means whereby the vacuolar system (a term which describes the shuttle and flow of lysosomal subgroups) is regulated. Since controlled hydrolysis of intracellular and extracellular macromolecules is the means whereby the cell handles foreign materials, processes antigens, remodels itself in cell division, and may indeed renew itself, these regulatory mechanisms deserve study. We will focus on those agents that regulate the flow of intracellular macromolecules from one compartment to the other, as well as those which act on membrane elements common to all components of the vacuolar system. Each regulatory factor will also be studied in a model, artificial system, recently devised, which bears many resemblances to natural biomembranes. BIBLIOGRAPHIC REFERENCES: Goldstein, I.M., Hoffstein, S.T. and Weissmann, G., Mechanisms of lysosomal enzyme release from human polymorphonuclear leukocytes: Effects of phorbol myristate acetate. J. Cell Biol. 66:647-652, 1975. Goldstein, I.M., Hoffstein, S.T. and Weissmann, G., Influence of divalent cations upon complement-mediated enzyme release from human polymorphonuclear leukocytes. J. Immunol. 115:665-670, 1975.